Pattern recognition receptor sensing double-stranded RNA (dsRNA-sensing PRR) (dsRNA-sensing PRR)

Pattern recognition receptors (PRRs) sensing double-stranded RNA (dsRNA) are a specialized group of innate immune sensors that detect viral infection and cellular distress (PubMed: 28234311). This class primarily includes the endosomal Toll-like receptor 3 (TLR3) and the cytosolic RIG-I-like receptors (RLRs), specifically RIG-I (DDX58) and MDA5 (IFIH1) (UniProt: O15455, O95786, Q9BYX4). These receptors recognize dsRNA of varying lengths and structural features, such as 5-triphosphate ends, which are characteristic of viral replication intermediates (PubMed: 30635013). Activation of these sensors triggers signaling pathways through adapter proteins like TRIF or MAVS, ultimately inducing the expression of Type I interferons and pro-inflammatory cytokines (PubMed: 24332152). In therapeutic contexts, dsRNA-sensing PRRs are targeted by synthetic RNA agonists like Poly(I:C) or rintatolimod to boost vaccine responses or stimulate anti-tumor immunity (PubMed: 31065105). However, dysregulation of these pathways is linked to autoimmune diseases like Aicardi-Goutières syndrome and chronic inflammatory conditions (PubMed: 25614466).

Other names

dsRNA sensorsDouble-stranded RNA receptorsCytosolic RNA sensorsRLRs and TLR3Toll-like receptor 3RIG-I-like receptorsMDA5RIG-I

Agonism of TLR3, RIG-I, or MDA5 to induce Type I interferon production and pro-inflammatory cytokine release for antiviral or antineoplastic effects; antagonism to mitigate autoimmune or autoinflammatory responses.